Ravi Tolwani, D.V.M, Ph.D. is a Diplomate of the American College of Laboratory Animal Medicine whose doctoral training with Dr. Phillip Wood at the University of Alabama, Birmingham, focused on the development of an animal model deficient in fatty acid oxidation using site-directed mutagenesis in embryonic stem cells. Since completing his Ph.D., Dr. Tolwani has been engaged in clinical laboratory animal care. Dr. Tolwani plans to build on this background in molecular genetics to develop his skills in the experimental manipulation of the mouse genome and the development of transgenic mouse models. Dr. Tolwani's research is co- sponsored by Linda Cork, D.V.M., Ph.D., a comparative neuropathologist with expertise in characterization of animal models, and Eric hooter, Ph.D., who has an outstanding reputation for his work on neurotrophins. Dr. Tolwani will work in two laboratories. Dr. Shooter has a cutting- edge cell and molecular biology laboratory and Dr. Cork has a specialized comparative neuropathology laboratory. Each laboratory will bring its particular strengths to the proposed research. Dr. Tolwani will analyze, in part, mechanisms which may protect neurons from excessive neurotrophins. Neurotrophins are secreted in minute amounts and support the survival and differentiation of neurons. Insufficient or excessive amounts of neurotrophins alters neuronal function and physiology. Transgenic mouse models will be developed in which expression of brain derived neurotrophic factor (BDNF) can be induced; these will be used to analyze specific molecular mechanisms which may protect against excessive BDNF. Transgenic mice will also be used to evaluate how changes in amounts of BDNF affect dopaminergic function an induced mouse model of Parkinson disease. This unique transgenic mouse model will be utilized to understand the biology of neurotrophins and to examine the therapeutic potential of neurotrophins for neurodegenerative disease.